Cancer is the second leading cause of death in the United States accounting for almost 500,000 deaths each year. More than 1,000,000 new cases of cancer are diagnosed in the United States annually. The incidence of cancer is increasing largely as a byproduct of the greater lifespan of the aging population. Cancer is a leading cause of death in all industrialized nations, where life expectancy continues to increase. It is expected that cancer morbidity and mortality will continue to increase in all industrialized areas of the world.
Prostate cancer is the most common malignancy among males in the U.S. accounting for 28% of all malignancies in men. It is estimated there will be 165, 000 new cases of prostate cancer in the United States in 1993 and 35,000 deaths (Boring, CC, et al CA Cancer J Clin (1993) 43:7-26).
Prostate cancer continues to be refractory to treatment despite many years of efforts to improve therapy. Surgery and radiation remain the mainstays of therapy; improved therapeutic modalities are needed. Vaccine development has been slow and no vaccine approved by the FDA for marketing currently exists for any form of cancer. There is therefore a continuing need for the development of new therapeutic and prophylactic compounds effective in the prevention and treatment of prostate cancer
The use of vaccines as cancer therapy is known (reviewed in Hoover, Jr. HC and Hanna, Jr. MG, Biological Therapy of Cancer (1991) Devita, Jr., DT, et al., eds. J. B. Lippincott Co., pp 670-701. There are many reports in the open literature of vaccines consisting of whole autologous or allogeneic tumor cells or their extracts formulated with bacterial adjuvants such as Bacillus-Calmette-Guerrin (BCG), Corynebacterium parvum or vaccinia virus. There has been no report of the use of an antigen unique to the prostate such as a prostate associated protein or an anti idiotypic antibody bearing the internal image of the prostate antigen as a vaccine for prostate cancer.
U.S. Pat. No. 3,960,827 describes a cancer-associated polypeptide antigen which is described as having a molecular weight of 20-27 kd and as associated with a number of types of cancers. The use of this antigen in antitumor vaccines is suggested. U.S. Pat. No. 4,372,945 discloses the use of tumor cells as secondary antigens in immunotherapeutic treatment of cancer. U.S. Pat. No. 4,446,122 discloses the use of prostate specific antigen (PSA) isolated from human tissue to prepare antibodies for tumor diagnosis. U.S. Pat. No. 4,468,457 describes the isolation of a colon specific antigen which is digested with trypsin to obtain a peptide used to produce monospecific antibodies against the antigen. U.S. Pat. No. 4,689,222 describes a method for alleviation of symptomatic pain associated with neoplasia by administering a low dose of human chorionic gonadotropin insufficient to provoke a humoral response. U.S. Pat. No. 4,877,611 describes vaccines containing tumor-associated antigens. The vaccines contain the tumor-associated antigen in the presence of specific adjuvants. PCT application WO91/11465 describes anticancer vaccines using antiidiotype antibodies that mimic an antigen produced by or associated with the malignant cell.
U.S. Pat. No. 5,053,224 issued Oct. 1, 1991 describes the preparation of both polyclonal and monoclonal anti idiotypic antibodies that recognize the paratope of an antitumor antibody. The issued patent further describes the use of these anti idiotypic antibodies generally to stimulate the production of anti anti idiotypic antibodies in tumor patients. Copending patent application No. 07/938,079 filed Aug. 31, 1992, now abandoned in favor of File Wrapper Continuation Ser. No. 08/185,313 filed Jan. 21, 1994 the disclosure of which is incorporated herein by reference discloses the use of anti idiotypic antibodies generally to stimulate an antitumor T cell response for prevention and/or therapy of cancer. Copending patent application No. 07/800,474 filed Nov. 26, 1991, now abandoned in favor of File Wrapper Continuation Serial No. 08/151,568 filed Nov. 12, 1993 the disclosure of which is incorporated herein by reference describes generally the use of pure tumor antigen encapsulated in or conjugated to liposomes for the treatment and prevention of cancer.
The present invention concerns the use of prostate antigens or their representatives in vaccines to produce an immune response to prevent or treat prostate cancer.